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Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy

    Deepika Singh

    Department of Molecular & Human Genetics, Cancer Genetics Laboratory, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    ,
    Mallika Tewari

    Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    ,
    Sunita Singh

    Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi, 221005, India

    &
    Gopeshwar Narayan

    *Author for correspondence:

    E-mail Address: gnarayan@bhu.ac.in

    Department of Molecular & Human Genetics, Cancer Genetics Laboratory, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Published Online:https://doi.org/10.2217/fon-2020-0727

    TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.

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